Pfizer.

of coronavirus disease (COVID-19) had been reported globally since December 2019 (1), severely burdening the healthcare system (2). The extremely fast transmission capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has aroused concern about its various transmission routes.The main transmission routes for SARS-CoV-2 are respiratory droplets and close contact (3). Knowing the extent of environmental contamination of SARS-CoV-2 in COVID-19 wards is critical for improving safety practices for medical staff and answering questions about SARS-CoV-2 transmission among the public. However, whether SARS-CoV-2 can be transmitted by aerosols remains controversial, and the exposure risk for close contacts has not been systematically evaluated. Researchers have detected SARS-CoV-2 on surfaces of objects in a symptomatic patient's room and toilet area (4). However, that study was performed in a small sample from regions with few confirmed cases, which might not reflect real conditions in outbreak regions where hospitals are operating at full capacity. In this study, we tested surface and air samples from an intensive care unit (ICU) and a general COVID-19 ward (GW) at Huoshenshan Hospital in Wuhan, China (Figure 1). The StudyFrom February 19 through March 2, 2020, we collected swab samples from potentially contaminated objects in the ICU and GW as described previously (5). The ICU housed 15 patients with severe disease and the GW housed 24 patients with milder disease. We also sampled indoor air and the air outlets to detect aerosol exposure. Air samples were collected by using a SASS 2300 Wetted Wall Cyclone Sampler (Research International, Inc., https://www.resrchintl.com) at 300 L/min for of 30 min. We used sterile premoistened swabs to sample the floors, computer mice, trash cans, sickbed handrails, patient masks, personal protective equipment, and air outlets. We tested air and surface samples for the open reading frame (ORF) 1ab and nucleoprotein (N) genes of SARS-CoV-2 by quantitative real-time PCR. (Appendix, https://wwwnc.cdc.gov/EID/ article/26/7/20-0885-App1.pdf).Almost all positive results were concentrated in the contaminated areas (ICU 54/57, 94.7%; GW 9/9, 100%); the rate of positivity was much higher for the ICU (54/124, 43.5%) than for the GW (9/114, 7.9%) (Tables 1, 2). The rate of positivity was

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BACKGROUNDApalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined. METHODSIn this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival. RESULTSA total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group. CONCLUSIONSIn this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the sideeffect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.

Current antiviral agents can control but not eliminate hepatitis B virus (HBV), because HBV establishes a stable nuclear covalently closed circular DNA (cccDNA). Interferon-α treatment can clear HBV but is limited by systemic side effects. We describe how interferon-α can induce specific degradation of the nuclear viral DNA without hepatotoxicity and propose lymphotoxin-β receptor activation as a therapeutic alternative. Interferon-α and lymphotoxin-β receptor activation up-regulated APOBEC3A and APOBEC3B cytidine deaminases, respectively, in HBV-infected cells, primary hepatocytes, and human liver needle biopsies. HBV core protein mediated the interaction with nuclear cccDNA, resulting in cytidine deamination, apurinic/apyrimidinic site formation, and finally cccDNA degradation that prevented HBV reactivation. Genomic DNA was not affected. Thus, inducing nuclear deaminases-for example, by lymphotoxin-β receptor activation-allows the development of new therapeutics that, in combination with existing antivirals, may cure hepatitis B.